Is ARSB p.Arg501His (c.1502G>A) pathogenic?

ARSB p.Arg501His (c.1502G>A) is classified Uncertain significance in ARSB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-07). AlphaMissense: likely benign (0.1367); Very rare (popmax 0.00891%, eas); Associated with mucopolysaccharidosis type 6.

What condition is associated with ARSB p.Arg501His (c.1502G>A)?

ARSB p.Arg501His (c.1502G>A) is associated with mucopolysaccharidosis type 6 (ClinVar).

How common is ARSB p.Arg501His (c.1502G>A) in the general population?

ARSB p.Arg501His (c.1502G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

How is Mucopolysaccharidosis type 6 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ARSB p.Arg501His (c.1502G>A)?

AlphaMissense predicts likely benign (score 0.1367) — an in-silico prediction, not a clinical call.

ARSB p.Arg501His

c.1502G>A · rs190643827 · VCV354304

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1367 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 6

Computational evidence

Protein change
AlphaMissense	0.1367	likely benign
REVEL	0.671	pathogenic-leaning
SaProt	LLR -12.49	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,878 alleles

Filtering AF 0.00495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00533% 86/1,614,052 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
European (non-Finnish)	0.0061%	16,389
African / African-American	0.00533%	18,747
South Asian	0.00329%	30,359
Remaining individualsnot grpmax-eligible	0.0032%	31,254
Admixed American	0.00167%	60,006

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ARSB
Protein: p.Arg501His
Coding: c.1502G>A
MANE Select: NM_020427 · reported on NM_000046
dbSNP: rs190643827
Type: single nucleotide variant
Location: chr5:78780497 (GRCh38)
Structure: AlphaFold pLDDT 84.32 · 2 PDB

Full ARSB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mucopolysaccharidosis type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mucopolysaccharidosis type 6 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ARSB c.1142+1G>A Pathogenic ★★ same condition
ARSB c.1142+1G>T Pathogenic ★★ same condition
ARSB c.1142+2T>A Pathogenic/Likely pathogenic ★★ same condition
ARSB c.1142+2T>C Pathogenic ★★ same condition
ARSB c.1143-1G>A Pathogenic/Likely pathogenic ★★ same condition
ARSB c.1143-1G>C Pathogenic ★★ same condition
ARSB c.1143-8T>G Pathogenic/Likely pathogenic ★★ same condition
ARSB c.1213+6T>C Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/arsb-p-arg501his (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown